Mechanism of Toxic Cell Death Flashcards
What are the mechanisms of toxic cell death?
Impaired ATP synthesis; alteration of Ca gradients; other mechanisms–damage to cell membrane, cytoskeleton, or protein synthesis
How can ATP synthesis be impaired?
interfering with delivery of electrons; delivery of oxygen; ETC function; ATP synthase inhibition; uncouplers
what impairs delivery of electrons?
i. Fluoracetate–inhibits aconitase in the CAC
ii. Used as to kill rodents
Can’t deliver e-s to ETC–>no ATP production
what impairs delivery of oxygen?
i. Carbon monoxide
ii. Outcompetes O2 for hemoglobin
iii. Blocks delivery of O2 to mitochondria for the ETC
what impairs ETC function?
i. E.g. cyanide
1) Inhibits cytochrome oxidase
ii. E.g. rotenone–inhibits NADH coenzyme Q reducase
what inihibts ATP synthase?
d. Chlordecone
i. Insectiside
Same class as DDT–can’t phos ADP to ATP
what are the uncouplers?
i. Disrupt proton gradient
ii. E.g. pesticide called pentachlorophenol (PCPs)
iii. Fungicide
iv. Dinitrophenols
what is pentachlorophenol?
???
what are fungicides and how do they disturb cell membranes?
iii. Fungicide
1) Treating for lumber
2) Washes off into streams, kills fish
3) “ionophore”–makes membrane leaky to protons
what are dinitrophenols?
1) Donate protons in inner mitochondrial space
Reduce the gradient
alteration of Ca gradients
iv. 10 000x more ECF Ca than ICF Ca
1) When you open up the Ca “dam”, Ca floods in
v. Main mechanism: xenos alter plasma membrane permeability to Ca
1) Damage to membrane, to active transport that pumps Ca out
Major target: mitochondrial Ca (not SR Ca
how do nonpolar solvents cause toxic cell death?
1) Lipid sol solvents
2) Alter the fluidity of membrane
a) E.g. like cholesterol
how can the cytoskeleton be destroyed?
1) Scaffolding
2) Cholchecine–destroys spindle fibres (important in cell divison–inhibits mitosis)
how can protein synthesis be interfered with?
1) Ethanol
a) This is why you don’t take tylenol with a hangover
b) If you have been binge drinking, protein synthesis has been shut down–>especially glutathione